liproxstatin-1 and Melanoma

The design of cancer-targeting particles with precisely tuned physicochemical properties may enhance the delivery of therapeutics and access to pharmacological targets. However, a molecular-level understanding of the interactions driving the fate of nanomedicine in biological systems remains elusive. Here, we show that ultrasmall (<10 nm in diameter) poly(ethylene glycol)-coated silica nanoparticles, functionalized with melanoma-targeting peptides, can induce a form of programmed cell death known as ferroptosis in starved cancer cells and cancer-bearing mice. Tumour xenografts in mice intravenously injected with nanoparticles using a high-dose multiple injection scheme exhibit reduced growth or regression, in a manner that is reversed by the pharmacological inhibitor of ferroptosis, liproxstatin-1. These data demonstrate that ferroptosis can be targeted by ultrasmall silica nanoparticles and may have therapeutic potential.

Topics: alpha-MSH; Amino Acids; Animals; Antineoplastic Agents; Cell Death; Cell Line, Tumor; Humans; Iron; Lysosomes; Melanoma; Mice; Mice, SCID; Nanoparticles; Particle Size; Polyethylene Glycols; Quinoxalines; Silicon Dioxide; Spiro Compounds; Xenograft Model Antitumor Assays